A 31-year-old woman with no significant past medical or family history was admitted with complaints of general weakness. Laboratory tests revealed: serum potassium 3.0 mEq/L, arterial blood pH 7.28, serum bicarbonate 17.8 mEq/L and urinary pH 7.0. Double-labeling confocal fluorescence microscopy using H(+)-ATPase and pendrin antibodies demonstrated a decreased expression of these proteins in the patient's renal collecting duct compared to normal controls. Anti-Sjögren's-syndrome-related antigen A (Anti-Ro/SS-A) and anti-Sjögren's syndrome type B (anti-La/SS-B) antibodies were strongly positive with very high titers, consistent with Sjögren's syndrome. We present a case of distal renal tubular acidosis-associated Sjögren's syndrome with a defect in H(+)-ATPase and pendrin in the renal collecting duct.